Effect of Trigeminal Nerve Stimulation on Corneal Nerves and Chronic Ocular Pain

NCT04648085 | Completed FDA Device

• 1 other identifier: CI-006-2020
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Individuals with dry eye tend to present with ocular pain which persists despite the use of topical treatment. This could be secondary to somatosensory impairment attributable to neuropathic pain. The purpose of this study is to evaluate the effect of trigeminal nerve stimulation (TNS) on corneal nerves and chronic ocular pain in patients with dry eye.

Conditions

Dry Eye; Neuropathic Pain; Eye Pain

Keywords

Transcutaneous Electric Stimulation; In vivo Confocal Microscopy; Subbasal Corneal Nerve Plexus; Dry Eye; Neuropathic Pain

Outcome Measures

Primary Outcomes (2)

• Identify the effect of trigeminal nerve stimulation on chronic eye pain in patients with dry eye.

  Eye pain will be evaluated prior to the use of trigeminal nerve stimulation using a numeric pain scale ranging from 0-10, "0" indicating no pain and "10" indicating the most severe pain imaginable. Pain will be evaluated posterior to therapy with trigeminal nerve stimulation with the same scale during monthly follow up.

  From three-six months

• Identify the effect of trigeminal nerve stimulation on subbasal corneal nerve plexus density in patients with dry eye.

  Initial subbasal corneal nerve plexus density will be measured prior to therapy with with in vivo confocal microscopy. Density measurements will be repeated every two months with in vivo confocal microscopy posterior to trigeminal nerve stimulation use.

  2 months- 6 months

Study Arms (1)

Pre and Post Treatment with Trigeminal Nerve Stimulation (TNS)

EXPERIMENTAL

Individuals will receive treatment with trigeminal nerve stimulation for 20 minutes at a frequency of 100 Hertz (Hz). Ocular pain intensity will be recorded prior and after the use of therapy.

Device: Trigeminal Nerve Stimulation

Interventions

Trigeminal Nerve Stimulation DEVICE

Applied to to the forehead using a self-adhesive electrode positioned bilaterally over the upper branches of the trigeminal nerve.The device generates electrical impulses allowing to stimulate the trigeminal nerve.

Pre and Post Treatment with Trigeminal Nerve Stimulation (TNS)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals with dry eye, Ocular pain for more than 3 months, Contact lens users, Individuals using topical treatment and/or systemic medication for dry eye syndrome, Individuals with history of photo-ablative ocular surgery (Laser-assisted in situ keratomileusis (LASIK) , Photorefractive keratectomy (PRK), Small incision lenticule extraction(SMILE), Individuals with history of autoimmune disease (Lupus, Rheumatoid Arthritis, Sjögrens),

You may not qualify if:

• Individuals with pacemakers or implantable defibrillators, Individuals with diagnosis of epilepsy, History of facial trauma one month prior to recruitment, Acute facial pain with unknown etiology, History of ocular surgery one month prior to recruitment, Trigeminal neuralgia, Active Herpes Zoster Ophthalmicus,

Sponsors & Collaborators

• Instituto de Oftalmología Fundación Conde de Valenciana: lead

Study Sites (1)

Instituto de Oftalmología Conde de Valenciana

Mexico City, Mexico City, 06800, Mexico

Location

Related Publications (22)

• Galor A, Moein HR, Lee C, Rodriguez A, Felix ER, Sarantopoulos KD, Levitt RC. Neuropathic pain and dry eye. Ocul Surf. 2018 Jan;16(1):31-44. doi: 10.1016/j.jtos.2017.10.001. Epub 2017 Oct 12.

  PMID: 29031645 BACKGROUND

• Craig JP, Nelson JD, Azar DT, Belmonte C, Bron AJ, Chauhan SK, de Paiva CS, Gomes JAP, Hammitt KM, Jones L, Nichols JJ, Nichols KK, Novack GD, Stapleton FJ, Willcox MDP, Wolffsohn JS, Sullivan DA. TFOS DEWS II Report Executive Summary. Ocul Surf. 2017 Oct;15(4):802-812. doi: 10.1016/j.jtos.2017.08.003. Epub 2017 Aug 8.

  PMID: 28797892 BACKGROUND

• De Paiva CS, Corrales RM, Villarreal AL, Farley WJ, Li DQ, Stern ME, Pflugfelder SC. Corticosteroid and doxycycline suppress MMP-9 and inflammatory cytokine expression, MAPK activation in the corneal epithelium in experimental dry eye. Exp Eye Res. 2006 Sep;83(3):526-35. doi: 10.1016/j.exer.2006.02.004. Epub 2006 Apr 27.

  PMID: 16643899 BACKGROUND

• Karson CN, Burns RS, LeWitt PA, Foster NL, Newman RP. Blink rates and disorders of movement. Neurology. 1984 May;34(5):677-8. doi: 10.1212/wnl.34.5.677.

  PMID: 6231489 BACKGROUND

• Dworkin RH, O'Connor AB, Kent J, Mackey SC, Raja SN, Stacey BR, Levy RM, Backonja M, Baron R, Harke H, Loeser JD, Treede RD, Turk DC, Wells CD. Interventional management of neuropathic pain: NeuPSIG recommendations. Pain. 2013 Nov;154(11):2249-2261. doi: 10.1016/j.pain.2013.06.004. Epub 2013 Jun 6.

  PMID: 23748119 BACKGROUND

• Kalangara JP, Galor A, Levitt RC, Covington DB, McManus KT, Sarantopoulos CD, Felix ER. Characteristics of Ocular Pain Complaints in Patients With Idiopathic Dry Eye Symptoms. Eye Contact Lens. 2017 May;43(3):192-198. doi: 10.1097/ICL.0000000000000249.

  PMID: 26925537 BACKGROUND

• Farhangi M, Feuer W, Galor A, Bouhassira D, Levitt RC, Sarantopoulos CD, Felix ER. Modification of the Neuropathic Pain Symptom Inventory for use in eye pain (NPSI-Eye). Pain. 2019 Jul;160(7):1541-1550. doi: 10.1097/j.pain.0000000000001552.

  PMID: 30883524 BACKGROUND

• Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000 Jun 9;288(5472):1765-9. doi: 10.1126/science.288.5472.1765.

  PMID: 10846153 BACKGROUND

• Crane AM, Feuer W, Felix ER, Levitt RC, McClellan AL, Sarantopoulos KD, Galor A. Evidence of central sensitisation in those with dry eye symptoms and neuropathic-like ocular pain complaints: incomplete response to topical anaesthesia and generalised heightened sensitivity to evoked pain. Br J Ophthalmol. 2017 Sep;101(9):1238-1243. doi: 10.1136/bjophthalmol-2016-309658. Epub 2017 Jan 18.

  PMID: 28100479 BACKGROUND

• Matsumoto Y, Ibrahim OMA. Application of In Vivo Confocal Microscopy in Dry Eye Disease. Invest Ophthalmol Vis Sci. 2018 Nov 1;59(14):DES41-DES47. doi: 10.1167/iovs.17-23602.

  PMID: 30481805 BACKGROUND

• Tavakoli M, Hossain P, Malik RA. Clinical applications of corneal confocal microscopy. Clin Ophthalmol. 2008 Jun;2(2):435-45. doi: 10.2147/opth.s1490.

  PMID: 19668734 BACKGROUND

• Zhang M, Chen J, Luo L, Xiao Q, Sun M, Liu Z. Altered corneal nerves in aqueous tear deficiency viewed by in vivo confocal microscopy. Cornea. 2005 Oct;24(7):818-24. doi: 10.1097/01.ico.0000154402.01710.95.

  PMID: 16160498 BACKGROUND

• Alhatem A, Cavalcanti B, Hamrah P. In vivo confocal microscopy in dry eye disease and related conditions. Semin Ophthalmol. 2012 Sep-Nov;27(5-6):138-48. doi: 10.3109/08820538.2012.711416.

  PMID: 23163268 BACKGROUND

• Kinard KI, Smith AG, Singleton JR, Lessard MK, Katz BJ, Warner JE, Crum AV, Mifflin MD, Brennan KC, Digre KB. Chronic migraine is associated with reduced corneal nerve fiber density and symptoms of dry eye. Headache. 2015 Apr;55(4):543-9. doi: 10.1111/head.12547. Epub 2015 Mar 31.

  PMID: 25828778 BACKGROUND

• Aggarwal S, Kheirkhah A, Cavalcanti BM, Cruzat A, Colon C, Brown E, Borsook D, Pruss H, Hamrah P. Autologous Serum Tears for Treatment of Photoallodynia in Patients with Corneal Neuropathy: Efficacy and Evaluation with In Vivo Confocal Microscopy. Ocul Surf. 2015 Jul;13(3):250-62. doi: 10.1016/j.jtos.2015.01.005. Epub 2015 Feb 20.

  PMID: 26045233 BACKGROUND

• Small LR, Galor A, Felix ER, Horn DB, Levitt RC, Sarantopoulos CD. Oral Gabapentinoids and Nerve Blocks for the Treatment of Chronic Ocular Pain. Eye Contact Lens. 2020 May;46(3):174-181. doi: 10.1097/ICL.0000000000000630.

  PMID: 31206369 BACKGROUND

• Sivanesan E, Levitt RC, Sarantopoulos CD, Patin D, Galor A. Noninvasive Electrical Stimulation for the Treatment of Chronic Ocular Pain and Photophobia. Neuromodulation. 2018 Dec;21(8):727-734. doi: 10.1111/ner.12742. Epub 2017 Dec 28.

  PMID: 29283468 BACKGROUND

• Noseda R, Burstein R. Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, cortical spreading depression, sensitization, and modulation of pain. Pain. 2013 Dec;154 Suppl 1:S44-53. doi: 10.1016/j.pain.2013.07.021. Epub 2013 Jul 25.

  PMID: 23891892 BACKGROUND

• Zayan K, Aggarwal S, Felix E, Levitt R, Sarantopoulos K, Galor A. Transcutaneous Electrical Nerve Stimulation for the Long-Term Treatment of Ocular Pain. Neuromodulation. 2020 Aug;23(6):871-877. doi: 10.1111/ner.13146. Epub 2020 Mar 20.

  PMID: 32196838 BACKGROUND

• Martinez JD, Galor A, Ramos-Betancourt N, Lisker-Cervantes A, Beltran F, Ozorno-Zarate J, Sanchez-Huerta V, Torres-Vera MA, Hernandez-Quintela E. Frequency and risk factors associated with dry eye in patients attending a tertiary care ophthalmology center in Mexico City. Clin Ophthalmol. 2016 Jul 21;10:1335-42. doi: 10.2147/OPTH.S106451. eCollection 2016.

  PMID: 27499613 BACKGROUND

• Galor A, Feuer W, Lee DJ, Florez H, Venincasa VD, Perez VL. Ocular surface parameters in older male veterans. Invest Ophthalmol Vis Sci. 2013 Feb 19;54(2):1426-33. doi: 10.1167/iovs.12-10819.

  PMID: 23385801 BACKGROUND

• Patel DV, McGhee CN. Mapping of the normal human corneal sub-Basal nerve plexus by in vivo laser scanning confocal microscopy. Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4485-8. doi: 10.1167/iovs.05-0794.

  PMID: 16303938 BACKGROUND

MeSH Terms

Conditions

Dry Eye Syndromes; Neuralgia; Eye Pain

Condition Hierarchy (Ancestors)

Lacrimal Apparatus Diseases; Eye Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Eye Manifestations

Study Officials

• Simran Mangwani Mordani, MD

  Instituto de Oftalmología Conde de Valenciana

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, open, single-arm pilot study without randomization.

Study Record Dates

• First Submitted: November 21, 2020
• First Posted: December 1, 2020
• Study Start: February 3, 2021
• Primary Completion: December 10, 2021
• Study Completion: December 10, 2021
• Last Updated: January 18, 2022

Record last verified: 2022-01

Locations

ME (1)